daratumumab: clinical use

Prescribing considerations

• Administration requires specialist supervision, reaction prophylaxis and access to emergency treatment; record the product name and batch number.
• Obtain hepatitis B serology before treatment and consider antiviral prophylaxis against herpes-zoster reactivation.
• Notify transfusion services before treatment; obtain baseline group, antibody screen and appropriate phenotype or genotype information.
• Consider additional respiratory prophylaxis and observation in patients with chronic obstructive pulmonary disease.
• For systemic AL amyloidosis, assess and monitor cardiac involvement carefully.

Contraindications and cautions

• Hypersensitivity to daratumumab or a formulation excipient.
• The subcutaneous formulation should not be given to patients with hereditary fructose intolerance because it contains sorbitol; the intravenous formulation also requires specific assessment of this risk.

Monitoring

• Full blood count, particularly neutrophils, platelets and haemoglobin.
• Clinical evidence of infection and administration-related reactions.
• Hepatitis B reactivation in seropositive patients during and after treatment.
• Disease markers, recognising interference with serum protein electrophoresis and immunofixation in IgG-kappa disease.
• Acute ocular symptoms, cardiopulmonary status where clinically indicated, and injection-site reactions.

Clinical pharmacology

Daratumumab is a human IgG1-kappa monoclonal antibody targeting CD38. It causes immune-mediated cell killing through complement activation, antibody-dependent cellular cytotoxicity and phagocytosis. Clearance is partly target-mediated; renal excretion and hepatic enzyme metabolism are not expected to be major elimination routes.

Formulation and product differences

• The subcutaneous product is a ready-to-use solution containing recombinant human hyaluronidase and is administered into the abdomen only.
• The intravenous product is a concentrate requiring dilution before infusion.
• Administration-related reactions occur with both formulations but were less frequent with the subcutaneous formulation in comparative studies.
• Only the selected subcutaneous product includes licensed indications for high-risk smouldering multiple myeloma and newly diagnosed systemic AL amyloidosis.

Solution for infusion

Route: Intravenous

Strengths: 20 mg/mL

Injection

Route: Parenteral

Strengths: 1800 mg